Brucine → (S)-1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid

HRID 1020985Notes

Reaction equation

HRID 1020985 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[C:13](=[O:14])[CH2:12][C:11]([CH2:18][C:19]([CH3:21])=[CH2:20])([C:15]([OH:17])=[O:16])[CH2:10]1.COC1C=C2[C@@]34[C@@H]5C[C@H]6C(CN5CC3)=CCO[C@H]3CC(=O)N([C@H]4[C@@H]63)C2=CC=1OC>CC(O)C>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[N:9]1[C:13](=[O:14])[CH2:12][C@:11]([CH2:18][C:19]([CH3:21])=[CH2:20])([C:15]([OH:17])=[O:16])[CH2:10]1

Participants

4

Reactant 2

HCID 442021BrucineHCID 670924761-(2,6-Dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid

Product 1

HCID 58218841(S)-1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid (prepared from step b, 9 g, 31.36 mmol) and brucine (12.37 g, 31.35 mmol) was added iPrOH (75 mL) and heated with stirring at 75° C. until it became a clear solution, which was then allowed to cool to room temperature slowly. The resulting white solid was filtered and discarded. The filtrate was then diluted with Et2O (100 mL) and washed with 2 N HCl (2×100 mL), dried (Na2SO4) and concentrated under reduced pressure to obtain (S)-1-(2,6-dimethyl-phenyl)-3-(2-methyl-allyl)-5-oxo-pyrrolidine-3-carboxylic acid (550 mg, enantiomeric ratio: 9:1, with the enantiomeric ratio determined using a RegisWhelk® chiral analytical column and 10% EtOH in hexanes isocratic solvent system, flow rate: 1 mL/min, 30 min run). Further recrystallization of the above carboxylic acid derivative from hot toluene/dioxane (9:1, 14 mL) enriched the enantiomeric ratio to 99.2:0.8 and afforded 430 mg of (S)-1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid.

Workup

  1. temperatureheated
  2. temperatureto cool to room temperature slowly
  3. filtrationThe resulting white solid was filtered
  4. additionThe filtrate was then diluted with Et2O (100 mL)
  5. washwashed with 2 N HCl (2×100 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6a72544d51f843218c7ab79b9e6aed5a
Source dataset
uspto-grants-2014_05
Patent number
US08716494B2

Reaction notes

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